Disease relevance of SFA1

• DHA toxicity did, however, not solely appear related to formaldehyde accumulation, because SFA1 overexpression only enhanced formaldehyde but not DHA tolerance [1].
• Here we have purified a single activity from Escherichia coli, Saccharomyces cerevisiae and mouse macrophages that metabolizes S-nitrosoglutathione (GSNO), and show that it is the glutathione-dependent formaldehyde dehydrogenase [2].
• The mutagenesis was based on the results of homology modelling of a NAD(+)-specific FDH from Saccharomyces cerevisiae (SceFDH) using the Pseudomonas sp.101 FDH (PseFDH) crystal structure as a template [3].

High impact information on SFA1

• Glutathione synthase (GSH1) deletion led to decreased DHA survival in agreement with the glutathione cofactor requirement for the SFA1-encoded activity [1].
• The ADH2 gene codes for the Arabidopsis glutathione-dependent formaldehyde dehydrogenase (FALDH), an enzyme involved in formaldehyde metabolism in eukaryotes [4].
• In the present work, we have investigated the potential role of FALDH in detoxification of exogenous formaldehyde [4].
• S-nitrosoglutathione reductase activity of human and yeast glutathione-dependent formaldehyde dehydrogenase and its nuclear and cytoplasmic localisation [5].
• A eukaryotic formate dehydrogenase (EC 1.2.1.2, FDH) with its substrate specificity changed from NAD(+) to NADP(+) has been constructed by introducing two single-point mutations, Asp(196)-->Ala (D196A) and Tyr(197)-->Arg (Y197R) [3].

Biological context of SFA1

• A 3.7 kb DNA fragment of yeast chromosome IV has been sequenced that contains the SFA gene which, when present on a multi-copy plasmid in Saccharomyces cerevisiae, confers hyper-resistance to formaldehyde [6].
• The open reading frame of SFA is 1158 bp in size and encodes a polypeptide of 386 amino acids [6].
• Overexpression of the SFA gene leads to enhanced consumption of formaldehyde, which is most probably the reason for the observed hyper-resistance phenotype [6].
• Molecular structure and genetic regulation of SFA, a gene responsible for resistance to formaldehyde in Saccharomyces cerevisiae, and characterization of its protein product [6].
• Promoter deletion studies with a SFA promoter-lacZ gene fusion construct revealed negative interference on expression of SFA by upstream sequences [6].

Associations of SFA1 with chemical compounds

• The Saccharomyces cerevisiae gene SFA1, encoding formaldehyde dehydrogenase, was placed under the control of the GPD1 promoter and CYC1 terminator [7].
• The upstream region between positions -145 and -172 is totally or partially responsible for control of inducibility of SFA by chemicals such as formaldehyde (FA), ethanol and methyl methanesulphonate [6].
• Secondary 15N isotope effects at the N-1 position of 3-acetylpyridine adenine dinucleotide have been determined, by using the internal competition technique, for horse liver alcohol dehydrogenase (LADH) with cyclohexanol as a substrate and yeast formate dehydrogenase (FDH) with formate as a substrate [8].
• These results indicated that FLD, but not FDH, is essential for growth of C. boidinii on methanol [9].
• Molecular characterization of the two genes SNQ and SFA that confer hyperresistance to 4-nitroquinoline-N-oxide and formaldehyde in Saccharomyces cerevisiae [10].

Other interactions of SFA1

• The SFA gene shares an 868 bp divergent promoter with UGX2 a gene of yet unknown function [6].
• In addition to SFA, the gene encoding the formaldehyde dehydrogenase Adh5, an enzyme most potent in formaldehyde de-toxification, we isolated a second plasmid that conferred a less pronounced but significant hyper-resistance to formaldehyde [11].
• SFA is predicted to code for a long-chain alcohol dehydrogenase (glutathione-dependent formaldehyde dehydrogenase) of the yeast S. cerevisiae [6].

Analytical, diagnostic and therapeutic context of SFA1

• Northern blot analysis of SNQ and SFA revealed poly(A)+ RNA transcripts of 2 kb and 1.7 kb, respectively [10].

References